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PW Kalivas, P Duffy, LA DuMars and C Skinner
Department of Veterinary Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman.
Daily cocaine injection into rodents produces a progressive increase in the motor stimulant effect of acute cocaine administration. In this study it was found that daily cocaine injection (15 mg/kg i.p. x 3 days) produced an enhanced motor stimulant response to acute cocaine injection. The behavioral augmentation was linear with regards to dose in horizontal activity and behavioral intensity rating, but was biphasic in vertical activity. Augmented vertical, but not horizontal, activity in response to acute cocaine was found to persist for 2 weeks after the last daily injection of cocaine. Acute injection of cocaine was found to significantly decrease the level of dopamine (DA) metabolites in the nucleus accumbens, striatum and A10 DA region. In rats pretreated with daily injections of cocaine (15 mg/kg i.p. x 3 days), an acute challenge of cocaine 14 days after the last daily injection produced a more consistent decrease in DA metabolites in the nucleus accumbens, striatum and prefrontal cortex compared to daily saline-pretreated rats. In contrast, daily cocaine treatment abolished the decrease in DA metabolites produced in the A10 region by an acute cocaine challenge. Acute injection with cocaine was found to significantly depress dopa accumulation in the A10 region, nucleus accumbens and striatum. This effect was abolished in the A10 region in rats pretreated 14 days previously with daily injections of cocaine (7.5, 15.0 or 30 mg/kg i.p. x 3 days), but remained intact in the nucleus accumbens and striatum, except after daily pretreatment with the highest dose of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)
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